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免疫检查点抑制剂癌症免疫治疗中的免疫介导性肝炎:自身免疫性肝炎和肝脏免疫学的经验教训。

Immune-Mediated Hepatitis During Immune Checkpoint Inhibitor cancer Immunotherapy: Lessons From Autoimmune Hepatitis and Liver Immunology.

机构信息

Département de médecine, Université de Montréal, Montréal, QC, Canada.

Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montréal, QC, Canada.

出版信息

Front Immunol. 2022 Jun 30;13:907591. doi: 10.3389/fimmu.2022.907591. eCollection 2022.


DOI:10.3389/fimmu.2022.907591
PMID:35844534
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9280269/
Abstract

Immune checkpoint inhibitors (ICI) are being increasingly used to successfully treat several types of cancer. However, due to their mode of action, these treatments are associated with several immune-related adverse events (irAEs), including immune-mediated autoimmune-like hepatitis in 5 to 10% of cases. The specific immune mechanism responsible for the development of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI) is currently unknown. This review summarizes the current knowledge on hepatic irAEs during cancer immunotherapy. It also addresses the clinical management of ILICI and how it is becoming an increasingly important clinical issue. Clinical, histological, and laboratory features of autoimmune hepatitis (AIH) and ILICI are compared, and their shared and distinctive traits are discussed in an effort to better understand the development of hepatic irAEs. Finally, based on the current knowledge of liver immunology and AIH pathogenesis, we propose a series of events that could trigger the observed liver injury in ICI-treated patients. This model could be useful in the design of future studies aiming to identify the specific immune mechanism(s) at play in ILICI and improve immune checkpoint inhibitor cancer immunotherapy.

摘要

免疫检查点抑制剂(ICI)被越来越多地用于成功治疗多种类型的癌症。然而,由于其作用模式,这些治疗与几种免疫相关的不良反应(irAE)相关,包括在 5%至 10%的病例中发生的免疫介导的自身免疫样肝炎。目前尚不清楚导致免疫检查点抑制剂(ILICI)引起的免疫介导性肝损伤的特定免疫机制。这篇综述总结了癌症免疫治疗期间肝 irAE 的现有知识。它还讨论了 ILICI 的临床管理以及它如何成为一个越来越重要的临床问题。比较了自身免疫性肝炎(AIH)和 ILICI 的临床、组织学和实验室特征,并讨论了它们的共同和独特特征,以努力更好地了解肝 irAE 的发展。最后,根据目前对肝脏免疫学和 AIH 发病机制的了解,我们提出了一系列可能导致在接受 ICI 治疗的患者中观察到的肝损伤的事件。该模型可用于设计旨在确定 ILICI 中发挥作用的特定免疫机制并改善免疫检查点抑制剂癌症免疫治疗的未来研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac5/9280269/0651307dbcd2/fimmu-13-907591-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac5/9280269/0651307dbcd2/fimmu-13-907591-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac5/9280269/0651307dbcd2/fimmu-13-907591-g001.jpg

相似文献

[1]
Immune-Mediated Hepatitis During Immune Checkpoint Inhibitor cancer Immunotherapy: Lessons From Autoimmune Hepatitis and Liver Immunology.

Front Immunol. 2022

[2]
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[3]
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[4]
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[5]
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[6]
Deciphering the Dynamic Complexities of the Liver Microenvironment - Toward a Better Understanding of Immune-Mediated liver Injury Caused by Immune Checkpoint Inhibitors (ILICI).

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[7]
[Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors].

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[8]
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[10]
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Cancer Rep (Hoboken). 2025-7

[2]
Oncohepatology: Navigating liver injury in the era of modern cancer therapy.

World J Hepatol. 2025-6-27

[3]
Case Report: Regenerative hepatic pseudotumor induced by tislelizumab in a lung cancer patient.

Front Immunol. 2025-5-30

[4]
Bibliometric analysis of traditional Chinese medicine in cancer treatment via immune system modulation (2015-2025).

Front Immunol. 2025-5-8

[5]
Time dependent predictors of cardiac inflammatory adverse events in cancer patients receiving immune checkpoint inhibitors.

Cardiooncology. 2025-4-28

[6]
Germline prediction of immune checkpoint inhibitor discontinuation for immune-related adverse events.

J Immunother Cancer. 2025-3-28

[7]
Eligibility Criteria in Advanced Urothelial Cancer Clinical Trials: An Assessment of Modernization and Inclusion.

Cancer Med. 2025-4

[8]
Risk comparison of adverse reactions between gemcitabine monotherapy and gemcitabine combined with albumin-bound paclitaxel in pancreatic cancer: insights from the FDA Adverse Event Reporting System (FAERS) database.

BMC Pharmacol Toxicol. 2025-3-19

[9]
Potential radiotherapy-related reactivation of immune checkpoint inhibitor hepatitis.

Strahlenther Onkol. 2025-2-4

[10]
Hepatobiliary complications of immune checkpoint inhibitors in cancer.

Explor Target Antitumor Ther. 2024

本文引用的文献

[1]
Retreatment With Immune Checkpoint Inhibitors After a Severe Immune-Related Hepatitis: Results From a Prospective Multicenter Study.

Clin Gastroenterol Hepatol. 2023-3

[2]
Mechanisms of immune checkpoint inhibitor-mediated liver injury.

Acta Pharm Sin B. 2021-12

[3]
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.

J Clin Oncol. 2021-12-20

[4]
Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis.

Hepatology. 2022-3

[5]
Autoantibodies in Patients With Immune-Related Adverse Events From Checkpoint Inhibitors: A Systematic Literature Review.

J Clin Rheumatol. 2022-3-1

[6]
Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study.

J Clin Oncol. 2021-9-20

[7]
Immune Checkpoint Inhibitor Associated Hepatotoxicity in Primary Liver Cancer Versus Other Cancers: A Systematic Review and Meta-Analysis.

Front Oncol. 2021-4-21

[8]
Activation and transcriptional profile of monocytes and CD8 T cells are altered in checkpoint inhibitor-related hepatitis.

J Hepatol. 2021-7

[9]
Liver Injury Caused by Green Tea Extract in PD-1 Mice: An Impaired Immune Tolerance Model for Idiosyncratic Drug-Induced Liver Injury.

Chem Res Toxicol. 2021-3-15

[10]
Clinical features of immune-mediated hepatotoxicity induced by immune checkpoint inhibitors in patients with cancers.

J Cancer Res Clin Oncol. 2021-6

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